Shared learning database

The Royal London Hospital, Barts Health NHS Trust
Published date:
May 2013

The HBsAg quantitative assay records the amount of hepatitis B surface antigen in a patient's blood. This, in combination with hepatitis B virus DNA (HBV DNA) testing, enables physicians to monitor and evaluate a patient's response to peginterferon alfa-2a therapy, and to stop treatment after 24 weeks if indicated.

Guidance the shared learning relates to:
Does the example relate to a general implementation of all NICE guidance?
Does the example relate to a specific implementation of a specific piece of NICE guidance?


Aims and objectives

Introducing the hepatitis B surface antigen (HBsAg) quantitative assay allowed physicians to discontinue peginterferon alfa-2a in patients who were not benefiting from the drug (or demonstrating no response to the drug), based on the recently published data around stopping rules for peginterferon alfa-2a.

The objective was to ensure optimum use of peginterferon alfa-2a, so patients without an ostensible response to treatment would not continue to be exposed unnecessarily to any adverse effects of the drug.

Reasons for implementing your project

Prior to integrating the HBsAg quantitative assay into our clinical practice, we relied exclusively on HBV DNA decline to predict response in chronic hepatitis B patients treated with peginterferon alfa-2a. However, monitoring HBV DNA decline alone was considered by many as inadequate to make decisions on stopping therapy. Consequently, treatment discontinuation was often restricted to those patients experiencing adverse effects while taking the drug.

In line with recently published studies, quantitative HBsAg titres alone or combined with HBV DNA enables us to select patients likely to respond more favourably to a 48-week course of peginterferon alfa-2a, in addition to identifying those patients unlikely to respond, in whom treatment can be discontinued with confidence based on the stopping rules.

Using the quantitative HBsAg test allows us to apply the stopping rules for peginterferon alfa 2a, as recommended in NICE clinical guideline 165. NICE recommends offering a 48-week course of peginterferon alfa-2a as a first-line treatment in adults with surface antigen-positive chronic hepatitis B and compensated liver disease. Before starting treatment, quantitative HBsAg levels should be recorded and the test repeated at 12, 24 and 48 weeks after the initiation of peginterferon alfa-2a to determine treatment response. Quantitative HBsAg levels combined with HBV DNA decline, will determine whether a patient continues on treatment for the full 48 week course. Oral anti-viral treatment is offered as second-line treatment to people who are removed from treatment with peginterferon alfa-2a.

By using the hepatitis B surface antigen quantitative assay test we are able to decide after 12 weeks (in selected patients) or 24 weeks of treatment, if a patient should stay on a course of peginterferon alfa-2a or discontinue the drug, based on published data around the stopping rules. This allows patients to discontinue the drug if there is likely to be no benefit and in doing so, removes them from any adverse effects of the drug.

When patients show an early response to peginterferon alfa-2a, as demonstrated by a decline in quantitative HBsAg, the treating physician can use this information to help support and encourage the patient to adhere to the full 48 week treatment course, in the face of sometimes difficult side-effects.

How did you implement the project

By engaging with our virologists, we were able to demonstrate that the test would be used routinely to improve patient care. Once it was agreed that the laboratory would invest in the necessary equipment, we were able to work with the virologists and the viral hepatitis team to integrate the test as part of our standard laboratory investigations. Once the equipment has been purchased the test is fully automated so easy to administer. However, the need to include quantitative standards in each run makes the test more expensive that the qualitative test.

The quantitative test is about 3 times more expensive than a standard HBsAg test and still needs to be performed as a batch rather than as a random access sample. The test is not made available on the menu locally to avoid unnecessary requests for the quantitative test by non-specialist users during routine hepatitis screening.

At present, all patients being treated with peginterferon alfa-2a undergo quantitative HBsAg testing to determine the pre-treatment levels of surface antigen. At 12 weeks the test is repeated to assess treatment response and decline in HBsAg. In those who remain on treatment beyond 12 weeks, the test is repeated again at 24 weeks, and if the results demonstrate a sub-optimal response treatment is discontinued in-line with the stopping rules. This allows an early and timely switch to oral anti-viral medications in those people in whom peginterferon alfa-2a is unlikely to result in a virological response.

Key findings

We use the test to guide treatment decisions. Quantitative HBsAg testing demonstrates both when peginterferon alfa-2a is providing some treatment benefit and when a virological response is unlikely.

In patients whose response at 12 or 24 weeks is less than the thresholds of the stopping rules (ie >20,000 IU/ml in HBeAg positive disease or <10% decline in HBsAg from baseline in HBeAg negative disease), peginterferon alfa-2a should be discontinued and those patients switched to an oral anti-viral agent. Based on the stopping rules we are discontinuing peginterferon alfa-2a in approximately 33% of patients.

Physicians can utilise quantitative HBsAg levels to guide patient management and individualise treatment strategies in chronic hepatitis B. This allows the treating Physician to support patients struggling with side-effects of treatment, where a favourable on-treatment response can be used to motivate patients to continue therapy and improve adherence to achieve better outcomes.

Key learning points

- Find out the costs to your organisation of carrying out the test. It is likely that these costs will be less than anticipated.
- Engage with virologists at your laboratory so that they understand why the test is being done and that you will be using the test routinely and regularly.
- Evidence for using the test to improve patient care can be found in the full NICE guideline (CG165).
- It is important to understand the stopping rules, as indicated in NICE guidance, and to explain these clearly.
- Utilise the stopping rules to improve and individualise patient care. Stopping rules are different for HBsAg positive and HBsAg negative patients.
- Explain that this test is not informing whether or not to use peginterferon alfa-2a as a first-line treatment, but is about switching to a different treatment earlier when there is clear evidence that peginterferon alfa-2a is not going to have any long-term benefit.

Contact details

Patrick Kennedy
Clinical Senior Lecturer and Consultant Hepatologist
The Royal London Hospital, Barts Health NHS Trust

Primary care
Is the example industry-sponsored in any way?